【Animal Modeling】-Protein Transformation Regulation Mechanism of Rat Skeletal Muscle Atrophy Induced by Hypoxia Exposure

  OBJECTIVE: To compare the expression of genes related to protein synthesis and decomposition in skeletal muscle of rats under hypoxia exposure and normoxia paired with hypoxic feeding intervention (semi-starvation state), in order to explore the possible mechanism of hypoxia-induced skeletal muscle atrophy.

  Methods: SD rats were divided into: ① normoxia normal diet group (group C); ② hypoxia normal diet group (H group), the oxygen concentration was 12.4%; ③ normoxia paired diet group (P group), the feeding amount was The food intake on the previous day of the H group. After 4 weeks of intervention, the body composition of the rats was measured, the soleus muscle (SOL) and the extensor digitorum longus (EDL) were taken, and the wet weight was measured; HE staining was used to observe the shape of muscle fibers, and the cross-sectional area of muscle fibers was calculated ( FCSA); WB tested the protein content of HIF1α, Akt, p-Akt and skeletal muscle protein synthesis and decomposition-related genes in skeletal muscle.

  Results: 1) Compared with group C, the body weight of rats in group H continued to decrease, and there was no significant difference between group P and group C; the food intake of group H (same as group P) decreased significantly at the beginning of the intervention, and there was no difference between the two groups at the later stage; (2) After the intervention, the body weight and total muscle mass of the rats in group H were significantly lower than those in groups C and P, and there was no difference between group P and group C; the wet weight of both muscles in group H was significantly lower than that in group C; EDL in group H was significantly lower than that in group C. The FCSA of group H was significantly lower than that of group C and group P; (3) HIF1α protein content in EDL of group H was significantly higher than that of group C; the ratio of p-Akt/Akt in SOL in group H and group P was significantly lower than that in group C; The protein content of mTOR and 4EBP1 was significantly lower than that in group C, the protein content of atrogin1, MuRF1, and beclin1 and the ratio of LC3II/I were significantly higher than those in group C. The protein content of MuRF1 in SOL in group H was significantly higher than that in groups C and P.

  Conclusions Hypoxia-induced skeletal muscle atrophy is induced by hypoxia-specific factors, manifested as decreased protein synthesis and increased breakdown of skeletal muscle proteins, mainly fast-twitch muscles, rather than decreased food intake under hypoxia.